O -Halogen-substituted arene linked selenium- N -heterocyclic carbene compounds induce significant cytotoxicity: Crystal structures and molecular docking studies

Synthesis of N-arylated benzimidazolium salts 1-2 , as stable N-heterocyclic Carbene (NHC) Sigma- donor lig-ands, was carried out by simple, facile and high yielding method. Respective Se-NHC compounds 3-4 were synthesized in water at 100 degrees C in open air environment using elemental selenium as reactant. Var-ious spectroscopic methods (FT-IR,1H and 13 C NMR) were used for characterization of the products. Sin-gle crystal of salt 2 was analyzed by x-rays crystallographic analysis. In-vitro anticancer studies of the products 1-4 were carried out against breast cancer cell line (MDA-MB-231), cervical cancer cell line from Henrietta Lacks (HeLa), human normal endothelial cell line (EA.hy926) and adenocarcinoma cell line (A549) using MTT assay and compared with a standard drug 5-Flourouracil (5FU). The products 1-4 showed IC50 values less than standard drug 5FU against MDA-MB-231. Against HeLa cell line, compound 2 and its complex 4 were more potent with IC50 value of 0.05 mu M and 0.082 mu M, respectively as com-pared with 5FU having IC50 value of 4.9 mu M. Against A549 cell line the products 1-2 showed good IC50 values while 3 was inactive with very high value of IC50 and 4 also showed good IC50 value of 19.02 mu M. Against EA.hy926 cell line, both the salts 1-2 showed more toxicity with lower IC50 values than selenium counterpart 3-4 . The docked conformation of VEGFA, EGF, COX1 and HIF with active conformation of selenium compounds 3-4 and 5FU revealed numerous potential interactions. The selenium adducts 3-4 were better with lower binding energies than 5FU, however, both showed almost same values of inhi-bition constants and binding energies against all proteins. Also, inhibition constants of compounds 3-4 were almost equal but less than 5FU.(c) 2022 Elsevier B.V. All rights reserved.

Automated summary

Stable N-heterocyclic Carbene (NHC) Sigma-donor ligands, N-arylated benzimidazolium salts 1-2, were synthesized in a simple, facile, and high-yielding method. Selenium adducts 3-4 were also synthesized using elemental selenium as a reactant. The synthesized compounds were characterized using spectroscopic methods and their anticancer activity was evaluated against different cancer cell lines. The docking analysis revealed potential interactions between the compounds and cancer-related proteins.